Minireview: The androgen receptor in breast tissues: Growth inhibitor, tumor suppressor, oncogene?

Molecular Endocrinology

Volumn 26, Issue 8, 2012, Pages 1252-1267

  Hickey, T E ^a   Robinson, J L L ^b,c   Carroll, J S ^b,c   Tilley, W D ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b Li Ka Shing Centre   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABIRATERONE; ANDROGEN; ANDROGEN RECEPTOR; BICALUTAMIDE; ESTROGEN; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FLUOXYMESTERONE; TAMOXIFEN; TESTOSTERONE; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; BREAST CANCER; BREAST DEVELOPMENT; BREAST METASTASIS; COHORT ANALYSIS; FEMALE; GROWTH INHIBITION; HIRSUTISM; HORMONE ACTION; HUMAN; INTRACELLULAR SIGNALING; MAMMARY GLAND; ONCOGENE; PHENOTYPE; PRIORITY JOURNAL;

ANDROGENS; ANIMALS; BREAST NEOPLASMS; ESTROGEN RECEPTOR ALPHA; FEMALE; GENES, TUMOR SUPPRESSOR; GROWTH INHIBITORS; HUMANS; MAMMARY GLANDS, HUMAN; ONCOGENES; RECEPTORS, ANDROGEN; SIGNAL TRANSDUCTION;

EID: 84864447342     PISSN: 08888809     EISSN: None     Source Type: Journal    
DOI: 10.1210/me.2012-1107     Document Type: Article

References (144)

1. Jordan VC 2009 A century of deciphering the control mechanisms of sex steroid action in breast and prostate cancer: the origins of targeted therapy and chemoprevention. Cancer Res 69:1243-1254
2. Jordan VC, Obiorah I, Fan P, Kim HR, Ariazi E, Cunliffe H, Brauch H 2011 The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities. Breast 20(Suppl 3):S1-S11
3. Yager JD, Davidson NE 2006 Estrogen carcinogenesis in breast cancer. N Engl J Med 354:270-282
4. Wagner RK, Gorlich L, Jungblut PW 1973 Dihydrotestosterone receptor in human mammary cancer. Acta Endocrinol Suppl (Copenh) 173:65
5. Horwitz KB, Zava DT, Thilagar AK, Jensen EM, McGuire WL 1978 Steroid receptor analyses of nine human breast cancer cell lines. Cancer Res 38:2434-2437
6. Allegra JC, Lippman ME, Thompson EB, Simon R, Barlock A, Green L, Huff KK, Do HM, Aitken SC 1979 Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer. Cancer Res 39:1447-1454
7. Goldenberg IS 1964 Testosterone propionate therapy in breast cancer. JAMA 188:1069-1072
8. Goldenberg IS, Hayes MA 1961 Hormonal therapy of metastatic female breast carcinoma. II. 2-Methyl dihydrotestosterone propionate. Cancer 14:705-706
9. Goldenberg IS, Sedransk N, Volk H, Segaloff A, Kelley RM, Haines CR 1975 Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group. Cancer 36:308-310
10. Talley RW, Haines CR, Waters MN, Goldenberg IS, Olson KB, Bisel HF 1973 A dose-response evaluation of androgens in the treatment of metastatic breast cancer. Cancer 32:315-320
11. Burger HG 2002 Androgen production in women. Fertil Steril 77(Suppl 4):S3-S5
12. Labrie F, Luu-The V, Labrie C, Bélanger A, Simard J, Lin SX, Pelletier G 2003 Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 24:152-182
13. Rothman MS, Carlson NE, Xu M, Wang C, Swerdloff R, Lee P, Goh VH, Ridgway EC, Wierman ME 2011 Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry. Steroids 76:177-182
14. Pike MC, Spicer DV, Dahmoush L, Press MF 1993 Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15:17-35
15. Grynberg M, Fanchin R, Dubost G, Colau JC, Brémont-Weil C, Frydman R, Ayoubi JM 2010 Histology of genital tract and breast tissue after long-term testosterone administration in a female-tomale transsexual population. Reprod Biomed Online 20:553-558
16. McNamara KM, Harwood DT, Simanainen U, Walters KA, Jimenez M, Handelsman DJ 2010 Measurement of sex steroids in murine blood and reproductive tissues by liquid chromatographytandem mass spectrometry. J Steroid Biochem Mol Biol 121:611-618
17. Li X 2010 Aromatase over expression transgenic murine models for aromatase inhibitor studies. Mol Hum Reprod 16:80-86
18. Li X, Strauss L, Mäkelä S, Streng T, Huhtaniemi I, Santti R, Poutanen M 2004 Multiple structural and functional abnormalities in the p450 aromatase expressing transgenic male mice are ameliorated by a p450 aromatase inhibitor. Am J Pathol 164: 1039-1048
19. Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A 2009 History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev 30:343-375
20. Dimitrakakis C, Zhou J, Wang J, Belanger A, LaBrie F, Cheng C, Powell D, Bondy C 2003 A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 10:292-298
21. Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA 2000 Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J 14:1725-1730
22. Eick GN, Thornton JW 2011 Evolution of steroid receptors from an estrogen-sensitive ancestral receptor. Mol Cell Endocrinol 334: 31-38
23. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J 1986 Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150-1154
24. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA 1997 Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 82:4258-4265
25. Tilley WD, Marcelli M, Wilson JD, McPhaul MJ 1989 Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci USA 86:327-331
26. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM 1988 Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240:327-330
27. Margolis RN, Evans RM, O'Malley BW 2005 The nuclear receptor signaling atlas: development of a functional atlas of nuclear receptors. Mol Endocrinol 19:2433-2436
28. Biddie SC, John S, Hager GL 2010 Genome-wide mechanisms of nuclear receptor action. Trends Endocrinol Metab 21:3-9
29. Tang Q, Chen Y, Meyer C, Geistlinger T, Lupien M, Wang Q, Liu T, Zhang Y, Brown M, Liu XS 2011 A comprehensive view of nuclear receptor cancer cistromes. Cancer Res 71:6940-6947
30. Hah N, Danko CG, Core L, Waterfall JJ, Siepel A, Lis JT, Kraus WL 2011 A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell 145:622-634
31. Wang D, Garcia-Bassets I, Benner C, Li W, Su X, Zhou Y, Qiu J, Liu W, Kaikkonen MU, Ohgi KA, Glass CK, Rosenfeld MG, Fu XD 2011 Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474:390-394
32. Augello MA, Hickey TE, Knudsen KE 2011 FOXA1: master of steroid receptor function in cancer. EMBO J 30:3885-3894
33. Anderson E, Clarke RB 2004 Steroid receptors and cell cycle in normal mammary epithelium. J Mammary Gland Biol Neoplasia 9:3-13
34. Curtis Hewitt S, Couse JF, Korach KS 2000 Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action. Breast Cancer Res 2:345-352
35. Bernardo GM, Lozada KL, Miedler JD, Harburg G, Hewitt SC, Mosley JD, Godwin AK, Korach KS, Visvader JE, Kaestner KH, Abdul-Karim FW, Montano MM, Keri RA 2010 FOXA1 is an essential determinant of ER expression and mammary ductal morphogenesis. Development 137:2045-2054
36. Yeh S, Hu YC, Wang PH, Xie C, Xu Q, Tsai MY, Dong Z, Wang RS, Lee TH, Chang C 2003 Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J Exp Med 198:1899-1908
37. Simanainen U, Gao YR, Walters KA, Watson G, Desai R, Jimenez M, Handelsman DJ 2012 Androgen resistance in female mice increases susceptibility to DMBA-induced mammary tumors. Horm Cancer 3:113-124
38. Walters KA, Simanainen U, Handelsman DJ 2010 Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models. Hum Reprod Update 16:543-558
39. Peters AA, Ingman WV, Tilley WD, Butler LM 2011 Differential effects of exogenous androgen and an androgen receptor antagonist in the periand postpubertal murine mammary gland. Endocrinology 152:3728-3737
40. Jääskeläinen J 2012 Molecular biology of androgen insensitivity. Mol Cell Endocrinol 352:4-12
41. Anderson E 2001 Ovarian steroids and control of proliferation in the normal human breast. Breast 10:273-278
42. Cheng G, Li Y, Omoto Y, Wang Y, Berg T, Nord M, Vihko P, Warner M, Piao YS, Gustafsson JA 2005 Differential regulation of estrogen receptor (ER) and ERβ in primate mammary gland. J Clin Endocrinol Metab 90:435-444
43. Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, Jindal S, Segara D, Jia L, Moore NL, Henshall SM, Birrell SN, Coetzee GA, Sutherland RL, Butler LM, Tilley WD 2009 Androgen receptor inhibits estrogen receptoractivity and is prognostic in breast cancer. Cancer Res 69:6131-6140
44. Cheng G, Weihua Z, Warner M, Gustafsson JA 2004 Estrogen receptors ER and ERβ in proliferation in the rodent mammary gland. Proc Natl Acad Sci USA 101:3739-3746
45. Clarke RB, Howell A, Potten CS, Anderson E 1997 Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 57:4987-4991
46. Russo J, Ao X, Grill C, Russo IH 1999 Pattern of distribution of cells positive for estrogen receptor and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res Treat 53:217-227
47. Lea OA, Kvinnsland S, Thorsen T 1989 Improved measurement of androgen receptors in human breast cancer. Cancer Res 49:7162-7167
48. Kuenen-Boumeester V, Van der Kwast TH, van Putten WL, Claassen C, van Ooijen B, Henzen-Logmans SC 1992 Immunohistochemical determination of androgen receptors in relation to oestrogen and progesterone receptors in female breast cancer. Int J Cancer 52:581-584
49. Isola JJ 1993 Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol 170:31-35
50. Hall RE, Aspinall JO, Horsfall DJ, Birrell SN, Bentel JM, Sutherland RL, Tilley WD 1996 Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer. Br J Cancer 74:1175-1180
51. Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H 2003 Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer 98:703-711
52. Cimino-Mathews A, Hicks JL, Illei PB, Halushka MK, Fetting JH, De Marzo AM, Park BH, Argani P 9 December 2011 Androgenreceptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy. Hum Pathol org/10.1016/j.humpath.2011.08.007
53. Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ 2003 Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120:725-731
54. Gonzalez LO, Corte MD, Vazquez J, Junquera S, Sanchez R, Alvarez AC, Rodriguez JC, Lamelas ML, Vizoso FJ 2008 Androgen receptor expression in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 8:149
55. Riva C, Dainese E, Caprara G, Rocca PC, Massarelli G, Tot T, Capella C, Eusebi V 2005 Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma. Virchows Arch 447:695-700
56. Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS 2010 Expression of androgen receptors in primary breast cancer. Ann Oncol 21:488-492
57. Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS, Viale G, Sapino A 2010 Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat 124:607-617
58. Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL, Mills GB, Hennessy BT 2009 Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 15:2472-2478
59. Park S, Koo JS, Kim MS, Park HS, Lee JS, Lee JS, Kim SI, Park BW, Lee KS 2011 Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol 22:1755-1762
60. Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM 2011 Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 17:1867-1874
61. Bièche I, Parfait B, Tozlu S, Lidereau R, Vidaud M 2001 Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene. Carcinogenesis 22:1521-1526
62. Suzuki T, Darnel AD, Akahira JI, Ariga N, Ogawa S, Kaneko C, Takeyama J, Moriya T, Sasano H 2001 5-reductases in human breast carcinoma: possible modulator of in situ androgenic actions. J Clin Endocrinol Metab 86:2250-2257
63. Chanplakorn N, Chanplakorn P, Suzuki T, Ono K, Wang L, Chan MS, Wing L, Yiu CC, Chow LW, Sasano H 2011 Increased 5-reductase type 2 expression in human breast carcinoma following aromatase inhibitor therapy: the correlation with decreased tumor cell proliferation. Horm Cancer 2:73-81
64. Suzuki T, Miki Y, Moriya T, Akahira J, Ishida T, Hirakawa H, Yamaguchi Y, Hayashi S, Sasano H 2007 5-Reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer 120:285-291
65. Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R 2010 Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol 23:205-212
66. Vranic S, Tawfik O, Palazzo J, Bilalovic N, Eyzaguirre E, Lee LM, Adegboyega P, Hagenkord J, Gatalica Z 2010 EGFR and HER-2/ neu expression in invasive apocrine carcinoma of the breast. Mod Pathol 23:644-653
67. He J, Peng R, Yuan Z, Wang S, Peng J, Lin G, Jiang X, Qin T 2012 Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol 29:406-410
68. Micello D, Marando A, Sahnane N, Riva C, Capella C, Sessa F 2010 Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast cancers. Virchows Arch 457:467-476
69. Tang D, Xu S, Zhang Q, Zhao W 2012 The expression and clinical significance of the androgen receptor and E-cadherin in triplenegative breast cancer. Med Oncol 29:526-533
70. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D 2000 Molecular portraits of human breast tumours. Nature 406:747-752
71. Sørlie T, Prou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL 2001 Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869-10874
72. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lønning PE, Brown PO, Børresen-Dale AL, Botstein D 2003 Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418-8423
73. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L 2005 Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678-5685
74. Haibe-Kains B, Desmedt C, Loi S, Culhane AC, Bontempi G, Quackenbush J, Sotiriou C 2012 A three-gene model to robustly identify breast cancer molecular subtypes. J Natl Cancer Inst 104: 311-325
75. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R 2005 Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24:4660-4671
76. O'Malley FP, Bane A 2008 An update on apocrine lesions of the breast. Histopathology 52:3-10
77. Honma N, Takubo K, Akiyama F, Sawabe M, Arai T, Younes M, Kasumi F, Sakamoto G 2005 Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast. Histopathology 47:195-201
78. Hall RE, Clements JA, Birrell SN, Tilley WD 1998 Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours. Br J Cancer 78:360-365
79. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL 2006 An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25:3994-4008
80. Sanga S, Broom BM, Cristini V, Edgerton ME 2009 Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med Genomics 2:59
81. Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C 2007 An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol 8:R157
82. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA 2011 Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750-2767
83. Birrell SN, Butler LM, Harris JM, Buchanan G, Tilley WD 2007Disruption of androgen receptor signaling by synthetic rogestins may increase risk of developing breast cancer. FASEB J 21:2285-2293
84. Dimitrakakis C, Bondy C 2009 Androgens and the breast. Breast Cancer Res 11:212
85. Somboonporn W, Davis SR 2004 Testosterone effects on the breast: implications for testosterone therapy for women. Endocr Rev 25:374-388
86. Kao J, Salari K, Bocanegra M, Choi YL, Girard L, Gandhi J, Kwei KA, Hernandez-Boussard T, Wang P, Gazdar AF, Minna JD, Pollack JR 2009 Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One 4:e6146
87. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo WL, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW 2006 A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10:515-527
88. Birrell SN, Bentel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD 1995 Androgens induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol 52:459-467
89. Cops EJ, Bianco-Miotto T, Moore NL, Clarke CL, Birrell SN, Butler LM, Tilley WD 2008 Antiproliferative actions of the synthetic androgen, mibolerone, in breast cancer cells are mediated by both androgen and progesterone receptors. J Steroid Biochem Mol Biol 110:236-243
90. Lapointe J, Fournier A, Richard V, Labrie C 1999 Androgens down-regulate bcl-2 protooncogene expression in ZR-75-1 human breast cancer cells. Endocrinology 140:416-421
91. Poulin R, Baker D, Labrie F 1988 Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line. Breast Cancer Res Treat 12:213-225
92. Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T 2002 Testosterone and 5-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol Endocrinol 16:113-120
93. Kandouz M, Lombet A, Perrot JY, Jacob D, Carvajal S, Kazem A, Rostene W, Therwath A, Gompel A 1999 Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol 69:463-471
94. Lippman M, Bolan G, Huff K 1976 The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4610-4618
95. Zava DT, McGuire WL 1978 Human breast cancer: androgen action mediated by estrogen receptor. Science 199:787-788
96. MacIndoe JH, Etre LA 1980 Androgens inhibit estrogen action in MCF-7 human breast cancer cells. Life Sci 27:1643-1648
97. Szelei J, Jimenez J, Soto AM, Luizzi MF, Sonnenschein C 1997 Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor. Endocrinology 138:1406-1412
98. Andò S, De Amicis F, Rago V, Carpino A, Maggiolini M, Panno ML, Lanzino M 2002 Breast cancer: from estrogen to androgen receptor. Mol Cell Endocrinol 193:121-128
99. Lanzino M, De Amicis F, McPhaul MJ, Marsico S, Panno ML, Andò S 2005 Endogenous coactivator ARA70 interacts with estrogen receptor (EŔ) and modulates the functional ER /androgen receptor interplay in MCF-7 cells. J Biol Chem 280:20421-20430
100. Macedo LF, Guo Z, Tilghman SL, Sabnis GJ, Qiu Y, Brodie A 2006 Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res 66:7775-7782
101. Hackenberg R, Hofmann J, Hölzel F, Schulz KD 1988 Stimulatory effects of androgen and antiandrogen on the in vitro proliferation of human mammary carcinoma cells. J Cancer Res Clin Oncol 114:593-601
102. Greeve MA, Allan RK, Harvey JM, Bentel JM 2004 Inhibition of MCF-7 breast cancer cell proliferation by 5-dihydrotestosterone; a role for p21(Cip1/Waf1). J Mol Endocrinol 32:793-810
103. Sikora MJ, Cordero KE, Larios JM, Johnson MD, Lippman ME, Rae JM 2009 The androgen metabolite 5-androstane-3β,17βdiol (3βAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance. Breast Cancer Res Treat 115:289-296
104. Roy R, Dauvois S, Labrie F, Belanger A 1992 Estrogen-stimulated glucuronidation of dihydrotestosterone in MCF-7 human breast cancer cells. J Steroid Biochem Mol Biol 41:579-582
105. Hu DG, Mackenzie PI 2009 Estrogen receptor, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17β-estradiol in MCF-7 cells. Mol Pharmacol 76:425-439
106. Harrington WR, Sengupta S, Katzenellenbogen BS 2006 Estrogen regulation of the glucuronidation enzyme UGT2B15 in estrogen receptor-positive breast cancer cells. Endocrinology 147:3843-3850
107. De Amicis F, Thirugnansampanthan J, Cui Y, Selever J, Beyer A, Parra I, Weigel NL, Herynk MH, Tsimelzon A, Lewis MT, Chamness GC, Hilsenbeck SG, Andò S, Fuqua SA 2010 Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat 121:1-11
108. Zava DT, McGuire WL 1977 Estrogen receptors in androgen-induced breast tumor regression. Cancer Res 37:1608-1610
109. Panet-Raymond V, Gottlieb B, Beitel LK, Pinsky L, Trifiro MA 2000 Interactions between androgen and estrogen receptors and the effects on their transactivational properties. Mol Cell Endocrinol 167:139-150
110. Risbridger GP, Davis ID, Birrell SN, Tilley WD 2010 Breast and prostate cancer: more similar than different. Nat Rev Cancer 10: 205-212
111. Lanzino M, Sisci D, Morelli C, Garofalo C, Catalano S, Casaburi I, Capparelli C, Giordano C, Giordano F, Maggiolini M, Andò S 2010 Inhibition of cyclin D1 expression by androgen receptor in breast cancer cells-identification of a novel androgen response element. Nucleic Acids Res 38:5351-5365
112. Scher HI, Buchanan G, Gerald W, Butler LM, Tilley WD 2004 Targeting the androgen receptor: improving outcomes for castration-resistant prostate cancer. Endocr Relat Cancer 11:459-476
113. Hall RE, Birrell SN, Tilley WD, Sutherland RL 1994 MDA-MB-453, an androgen-responsive human breast carcinoma cell line with high level androgen receptor expression. Eur J Cancer 30A: 484-490
114. Naderi A, Hughes-Davies L 2008 A functionally significant cross talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer. Neoplasia 10:542-548
115. Robinson JL, Macarthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, Carroll JS 2011 Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO J 30:3019-3027
116. Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS 2011 FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet 43:27-33
117. Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M 2011 Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell 20:119-131
118. Chia KM, Liu J, Francis GD, Naderi A 2011 A feedback loop between androgen receptor and ERK signaling in estrogen receptor-negative breast cancer. Neoplasia 13:154-166
119. Naderi A, Chia KM, Liu J 2011 Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer. Breast Cancer Res 13:R36
120. Naderi A, Liu J 2010 Inhibition of androgen receptor and Cdc25A phosphatase as a combination targeted therapy in molecular apocrine breast cancer. Cancer Lett 298:74-87
121. Wang Y, Romigh T, He X, Tan MH, Orloff MS, Silverman RH, Heston WD, Eng C 2011 Differential regulation of PTEN expression by androgen receptor in prostate and breast cancers. Oncogene 30:4327-4338
122. Hackenberg R, Lüttchens S, Hofmann J, Kunzmann R, Hölzel F, Schulz KD 1991 Androgen sensitivity of the new human breast cancer cell line MFM-223. Cancer Res 51:5722-5727
123. Lin Fde M, Pincerato KM, Bacchi CE, Baracat EC, Carvalho FM 2012 Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity. J Clin Pathol 65:64-68
124. Toth-Fejel S, Cheek J, Calhoun K, Muller P, Pommier RF 2004 Estrogen and androgen receptors as comediators of breast cancer cell proliferation: providing a new therapeutic tool. Arch Surg 139:50-54
125. Hardin C, Pommier R, Calhoun K, Muller P, Jackson T, Pommier S 2007 A new hormonal therapy for estrogen receptor-negative breast cancer. World J Surg 31:1041-1046
126. Vranic S, Gatalica Z, Wang ZY 2011 Update on the molecular profile of the MDA-MB-453 cell line as a model for apocrine breast carcinoma studies. Oncol Lett 2:1131-1137
127. Vranic S, Gatalica Z, Deng H, Frkovic-Grazio S, Lee LM, Gurjeva O, Wang ZY 2011 ER36, a novel isoform of ER66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast. J Clin Pathol 64:54-57
128. Honma N, Saji S, Kurabayashi R, Aida J, Arai T, Horii R, Akiyama F, Iwase T, Harada N, Younes M, Toi M, Takubo K, Sakamoto G 2008 Oestrogen receptor-β1 but not oestrogen receptor-βcx is of prognostic value in apocrine carcinoma of the breast. APMIS 116:923-930
129. Charn TH, Liu ET, Chang EC, Lee YK, Katzenellenbogen JA, Katzenellenbogen BS 2010 Genome-wide dynamics of chromatin binding of estrogen receptors and β: mutual restriction and competitive site selection. Mol Endocrinol 24:47-59
130. Grober OM, Mutarelli M, Giurato G, Ravo M, Cicatiello L, De Filippo MR, Ferraro L, Nassa G, Papa MF, Paris O, Tarallo R, Luo S, Schroth GP, Benes V, Weisz A 2011 A Global analysis of estrogen receptor β binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor for target gene regulation. BMC Genomics 12:36
131. Manni A, Arafah BM, Pearson OH 1981 Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer. Cancer 48:2507-2509
132. Ingle JN, Suman VJ, Mailliard JA, Kugler JW, Krook JE, Michalak JC, Pisansky TM, Wold LE, Donohue JH, Goetz MP, Perez EA 2006 Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52. Breast Cancer Res Treat 98:217-222
133. Rose C, Kamby C, Mouridsen HT, Andersson M, Bastholt L, Møller KA, Andersen J, Munkholm P, Dombernowsky P, Christensen IJ 2000 Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer. A randomized trial of tamoxifen vs. tamoxifen aminoglutethimide and hydrocortisone and tamoxifen fluoxymesterone in women above 65 years of age. Breast Cancer Res Treat 61:103-110
134. Tormey DC, Simon RM, Lippman ME, Bull JM, Myers CE 1976 Evaluation of tamoxifen dose in advanced breast cancer: a progress report. Cancer Treat Rep 60:1451-1459
135. Tormey DC, Lippman ME, Edwards BK, Cassidy JG 1983 Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med 98:139-144
136. Tormey DC, Gelman R, Band PR, Sears M, Bauer M, Arseneau JC, Falkson G 1981 A prospective evaluation of chemohormonal therapy remission maintenance in advanced breast cancer. Breast Cancer Res Treat 1:111-119
137. Barone I, Brusco L, Fuqua SA 2010 Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res 16:2702-2708
138. Lønning PE 2009 Additive endocrine therapy for advanced breast cancer: back to the future. Acta Oncol 48:1092-1101
139. Tiefenbacher K, Daxenbichler G 2008 The role of androgens in normal and malignant breast tissue. Breast Care (Basel) 3:325-331
140. Harrell JC, Dye WW, Allred DC, Jedlicka P, Spoelstra NS, Sartorius CA, Horwitz KB 2006 Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes. Cancer Res 66:9308-9315
141. Zheng WQ, Lu J, Zheng JM, Hu FX, Ni CR 2001 Variation of ER status between primary and metastatic breast cancer and relationship to p53 expression*. Steroids 66:905-910
142. Butler JA, Trezona T, Vargas H, State D 1989 Value of measuring hormone receptor levels of regional metastatic carcinoma of the breast. Arch Surg 124:1131-1134; discussion 1134-1135
143. Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, Brown GD, Gojis O, Ellis IO, Green AR, Ali S, Chin SF, Palmieri C, Caldas C, Carroll JS 2012 Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481:389-393
144. Knudsen KE, Penning TM 2010 Partners in crime: deregulation of AR activity and androgen synthesis In prostate cancer. Trends Endocrinol Metab 21:315-324